TGF-Β superfamily receptors-Targets for antiangiogenic therapy?

The tgf- pathway controls a broad range of cellular behavior including cell proliferation,differentiation,and apoptosis of various cell types including tumor cells,endothelial cells,immune cells,and fibroblasts. besides tgf-β's direct effects on tumor growth and its involvement in neoangiogenesis have received recent attention. germline mutations in tgf- receptors or coreceptors causing hereditary hemorrhagic teleangiectasia and the loeys-dietz syndrome underline the involvement of tgf- in vessel formation and maturation. several therapeutic approaches are evaluated at present targeting the tgf- pathway including utilization of antisense oligonucleotides against tgf- itself or antibodies or small molecule inhibitors of tgf- receptors. some of these therapeutic agents have already entered the clinical arena including an antibody against the endothelium specific tgf- class i receptor alk-1 targeting tumor vasculature. in conclusion,therapeutic manipulation of the tgf- pathway opens great opportunities in future cancer therapy. © 2010 jasmin otten et al.